Synthetic and hydrolytic activities of classical D-glucose-6- phosphate phosphohydrolase (EC 3.1.3.9) are being studied in detail. Particular emphasis is being placed on comparative and developmental biochemical aspects. Catalytic properties and mechanisms of biological control are being studied in detail. Attempts are being made to characterize catalytically the enzyme from a variety of sources, to purify the enzyme, to assess its physiological phosphorylative potential, to elucidate factors regulating both synthetic and hydrolytic activities of the catalyst in vivo, and to establish its physiological roles in various animals in health and in disease (diabetes in particular). Attempts are being made to integrate synthetic activities of this enzyme, along with hepatic hexokinase and glucokinase, in a generalized mechanism for regulation, at the hepatic level, of blood glucose concentrations to meet the immediate metabolic demands of the organism under varying states of stress.